Liver Cancer
Conditions
Keywords
proton beam radiation
Brief summary
In this study the investigators will be studying the effects of proton beam radiation therapy. This is a very accurate kind of treatment that has been shown to affect less normal tissue than a photon radiation beam. The accuracy allows the investigators to more safely increase the amount of radiation delivered to eliminate cancer. This accuracy will potentially reduce side effects that participants would normally experience using photon radiation therapy. The purpose of this study is to determine if radiation using proton beam therapy will kill the cancer cells in the participants liver.
Detailed description
* Participants will receive treatment as an outpatient in the Francis H. Burr Proton Center at the Massachusetts General Hospital, the MD Anderson Proton Therapy Center or the Roberts Proton Therapy Center at the University of Pennsylvania. * Not everyone who participates in this study will be receiving the same dose of radiation. The dose received will be determined by the location of the tumor(s) within the liver. * Proton Beam radiation therapy to the liver will be given once a day, 5 days a week (Monday-Friday), for 2 weeks. * The following procedures will be performed once a week during treatment on days 1, 8 and 15, as well as on the last day of radiation: physical examination and blood tests.
Interventions
RADIATIONProton Beam Irradiation
Given once a day, 5 days a week, for 3 weeks
Sponsors
Dana-Farber Cancer Institute
Brigham and Women's Hospital
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
University of Pennsylvania
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Biopsy proven unresectable or locally recurrent hepatocellular cancer or intrahepatic cholangiocarcinoma. Patients with a single lesion must be 12cm or less in greatest dimension. For patients with two lesions, no lesion may be greater than 10cm in greatest dimension. For patients with three lesions, no lesion may be greater than 6cm in greatest dimension. Patients may have single or multinodular tumors (up to 3). There must be no evidence of extrahepatic tumor. Portal vein involvement or thrombosis is allowed. * Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as 20mm or greater with conventional techniques or as 10mm or greater with spiral CT scan. * Patients may have had prior chemotherapy, targeted biological therapy, surgery, transarterial chemoembolization (TACE), radiofrequency ablation, or cryosurgery for their disease as long as it is greater than 4 weeks from first protocol radiation treatment (6 weeks for nitrosoureas or mitomycin C). Patients may not have had prior radiation to the affected area. * 18 years of age or older * Expected survival must be greater than three months * ECOG Performance Status of 0, 1 or 2 * Normal organ and marrow function as outlined in the protocol * If patient has underlying cirrhosis, only Child-Pugh classification Group A or Group B patients should be included in this study. * Patients must be either surgically sterile or post-menopausal. Male and female patients of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of the study participation. * Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin
Exclusion criteria
* Women who are pregnant or lactating * Patients with evidence of non-hepatic metastatic disease * Local conditions or systemic illnesses which would reduce the local tolerance to radiation treatment, such as serious local injuries, active collagen vascular disease, etc. * Prior liver directed radiation treatment * Patients may have no serious medical illness, which may limit survival to less than 3 months * Patients may have no serious psychiatric illness/social situations which would limit compliance with study requirements * Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier * Patients may not be receiving any other study agents * Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 2 Year Local Control Rate | 2 years | The percentage of participants with local control after two years as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. The duration of control was measured from the start of treatment. Local control is the absence of local failure. Local Failure is defined as evidence of tumor growth/regrowth in any direction beyond that present of the pre-treatment imaging studies in the treated lesion(s). |
| Median Overall Survival | 5 years | The median survival time in months as measured from the start of treatment until death due to any cause or until the participants is censored. Participants are censored at the date of their last follow-up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Related Adverse Events ≥ Grade 3 | 2 years | Summary of the proton radiation related grade 3 or greater adverse events that participants experienced. Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE v3). |
| Patterns of Failure | 2 years | A summary of the patterns of treatment failure, shown as the number of participants that fall into each category at the end of study follow-up |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Proton Beam Irradiation This is a single arm study. All study participants will receive proton radiation therapy.
Proton Beam Irradiation: Given once a day, 5 days a week, for 3 weeks | 83 |
| Total | 83 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Liver Transplant | 1 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Progressive Disease | 1 |
| Overall Study | Protocol Violation | 1 |
Baseline characteristics
| Characteristic | Proton Beam Irradiation |
|---|---|
| Age, Continuous | 67.6 years |
| Child-Turcotte-Pugh Class A | 66 Participants |
| Child-Turcotte-Pugh Class B | 15 Participants |
| Child-Turcotte-Pugh Class C | 0 Participants |
| Child-Turcotte-Pugh Class No Cirrhosis | 4 Participants |
| Disease Status Locally Recurrent | 5 Participants |
| Disease Status Newly Diagnosed | 78 Participants |
| ECOG Performance Status 0 | 28 Participants |
| ECOG Performance Status 1 | 52 Participants |
| ECOG Performance Status 2 | 3 Participants |
| Number of Nodular Tumors 1 | 66 Participants |
| Number of Nodular Tumors 2 | 15 Participants |
| Number of Nodular Tumors 3 | 4 Participants |
| Previous Therapy Any chemotherapy | 27 Participants |
| Previous Therapy Any other | 15 Participants |
| Previous Therapy Any radiofrequency ablation | 2 Participants |
| Previous Therapy Any surgical resection | 4 Participants |
| Previous Therapy Any transarterial chemoembolization | 5 Participants |
| Previous Therapy None | 45 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Black | 4 Participants |
| Race/Ethnicity, Customized Hispanic (white or black) | 1 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants |
| Race/Ethnicity, Customized White | 76 Participants |
| Region of Enrollment United States | 83 participants |
| Sex: Female, Male Female | 32 Participants |
| Sex: Female, Male Male | 51 Participants |
| Underlying Liver Disease Hepatitis C Virus (HCV) (± Others) | 28 Participants |
| Underlying Liver Disease No HCV but Hepatitis B Virus (HBV) (± Others) | 6 Participants |
| Underlying Liver Disease No HCV/HBV but Ethyl Hepatocellularalcohol (EtOH) | 8 Participants |
| Underlying Liver Disease No HCV/HBV/EtOH but nonalcoholic steatohepatitis | 3 Participants |
| Underlying Liver Disease None | 36 Participants |
| Underlying Liver Disease Other | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 11 / 83 |
| other Total, other adverse events | 81 / 83 |
| serious Total, serious adverse events | 8 / 83 |
Outcome results
Primary
2 Year Local Control Rate
The percentage of participants with local control after two years as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. The duration of control was measured from the start of treatment. Local control is the absence of local failure. Local Failure is defined as evidence of tumor growth/regrowth in any direction beyond that present of the pre-treatment imaging studies in the treated lesion(s).
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Proton Beam Irradiation | 2 Year Local Control Rate | 94.4 percentage of participants |
Primary
Median Overall Survival
The median survival time in months as measured from the start of treatment until death due to any cause or until the participants is censored. Participants are censored at the date of their last follow-up.
Time frame: 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Proton Beam Irradiation | Median Overall Survival | 49.9 Months |
Secondary
Number of Participants With Treatment Related Adverse Events ≥ Grade 3
Summary of the proton radiation related grade 3 or greater adverse events that participants experienced. Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE v3).
Time frame: 2 years
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Proton Beam Irradiation | Number of Participants With Treatment Related Adverse Events ≥ Grade 3 | Liver Failure | 1 Participants |
| Proton Beam Irradiation | Number of Participants With Treatment Related Adverse Events ≥ Grade 3 | Platelets | 1 Participants |
| Proton Beam Irradiation | Number of Participants With Treatment Related Adverse Events ≥ Grade 3 | Ascites (nonmalignant) | 1 Participants |
| Proton Beam Irradiation | Number of Participants With Treatment Related Adverse Events ≥ Grade 3 | Ulcer, GI - stomach | 1 Participants |
| Proton Beam Irradiation | Number of Participants With Treatment Related Adverse Events ≥ Grade 3 | Bilirubin (hyperbilirubinemia) | 1 Participants |
Secondary
Patterns of Failure
A summary of the patterns of treatment failure, shown as the number of participants that fall into each category at the end of study follow-up
Time frame: 2 years
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Proton Beam Irradiation | Patterns of Failure | Isolated local failure | 5 Participants |
| Proton Beam Irradiation | Patterns of Failure | Dead of disease, no progression | 2 Participants |
| Proton Beam Irradiation | Patterns of Failure | Alive, no progression | 26 Participants |
| Proton Beam Irradiation | Patterns of Failure | Distant metastases | 38 Participants |
| Proton Beam Irradiation | Patterns of Failure | Local failure and distant metastases | 3 Participants |
| Proton Beam Irradiation | Patterns of Failure | Dead of other causes, no progression | 9 Participants |